Dermcidin

Dermcidin
Solution structure of dermcidin-1L.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2KSG​, 2YMK​
Identifiers
Symbols	DCD ; AIDD; DCD-1; DSEP; HCAP; PIF
External IDs	OMIM: 606634 HomoloGene: 89039 GeneCards: DCD Gene
Gene ontology Molecular function • protein binding • peptidase activity • poly(A) RNA binding Cellular component • extracellular region • extracellular exosome Biological process • proteolysis • killing of cells of other organism • defense response to bacterium • defense response to fungus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	117159	n/a
Ensembl	ENSG00000161634	n/a
UniProt	P81605	n/a
RefSeq (mRNA)	NM_001300854	n/a
RefSeq (protein)	NP_001287783	n/a
Location (UCSC)	Chr 12: 54.64 – 54.65 Mb	n/a
PubMed search		n/a

Dermcidin is a protein that in humans is encoded by the DCD gene,^[2][3] and is an anti-microbial (antibiotic) peptide secreted by human eccrine sweat glands onto the skin as a part of the innate host defense of the immune system.

Function

Dermcidin is a secreted protein that is subsequently processed into mature peptides of distinct biological activities. The C-terminal peptide is constitutively expressed in sweat and has antibacterial and antifungal activities. The N-terminal peptide, also known as diffusible survival evasion peptide, promotes neural cell survival under conditions of severe oxidative stress. A glycosylated form of the N-terminal peptide may be associated with cachexia (muscle wasting) in cancer patients.^[3]

      Survival evasion peptide                            Antimicrobial peptide

YDPEAASAPGSGNPCHEASAAQKENAGEDPGLARQAPKPRKQRSSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL 

The C-termial precursor DCD-1L is a 48 residue peptide that shows partial helicity in solution, as evidenced by the determination of its solution structure by NMR and CD-spectroscopy. The full length precursor is processed by undetermined proteases present in human sweat, to form several shorter peptides that show variable antimicrobial activity, named according to their C-terminal triplet of amino acids and their resiude length. One such active peptide is SSL25, which shows a 2-fold increase in activity against E.coli compared to DCD-1L.^[4]

DCD-1L SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL
DCD-1  SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSV
SSL25  SSLLEKGLDGAKKAVGGLGKLGKDA

Mechanism

The crystal structure of dermcidin has been solved in solution to reveal a hexameric helix-bundle, mediated by Zn ion binding.^[5] This is observed to form a tilted channel in membranes under computational examination by molecular dynamics simulations, and one suggested mechanism of antimicrobial action inferred from this observation is by ion gradient decoupling across biological membranes. This is supported by concurrent observations in experimental studies of a voltage dependent depolarization of lipid bilayers.

References

1. PDB: 2KSG​; Jung HH, Yang ST, Sim JY, Lee S, Lee JY, Kim HH, Shin SY, Kim JI (May 2010). "Analysis of the solution structure of the human antibiotic peptide dermcidin and its interaction with phospholipid vesicles". BMB Rep 43 (5): 362–8. doi:10.3858/bmbrep.2010.43.5.362. PMID 20510021.
2. Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, Schirle M, Schroeder K, Blin N, Meier F, Rassner G, Garbe C (Nov 2001). "Dermicidin: a novel human antibiotic peptide secreted by sweat glands". Nat Immunol 2 (12): 1133–7. doi:10.1038/ni732. PMID 11694882.
3. "Entrez Gene: DCD dermcidin".
4. Baechle D, Flad T, Cansier A; et al. (2006). "Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L.". J. Biol. Chem. 281 (9): 5406–15. doi:10.1074/jbc.M504670200. PMID 16354654.
5. PDB: 2YMK​Song, Chen; Weichbrodt, Conrad; Salnikov, Evgeniy S; Dynowski, Marek; Forsberg, Björn O; Bechinger, Burkhard; Steinem, Claudia; de Groot, Bert L; Zachariae, Ulrich; Zeth, Kornelius (Feb 2013). "Crystal structure and functional mechanism of a human antimicrobial membrane channel". PNAS 110 (12): 4586–91. doi:10.1073/pnas.1214739110. PMID 23426625.

Further reading

• Todorov P, Cariuk P, McDevitt T; et al. (1996). "Characterization of a cancer cachectic factor.". Nature 379 (6567): 739–42. doi:10.1038/379739a0. PMID 8602222.
• Todorov PT, Deacon M, Tisdale MJ (1997). "Structural analysis of a tumor-produced sulfated glycoprotein capable of initiating muscle protein degradation.". J. Biol. Chem. 272 (19): 12279–88. doi:10.1074/jbc.272.19.12279. PMID 9139670.
• Cunningham TJ, Hodge L, Speicher D; et al. (1998). "Identification of a survival-promoting peptide in medium conditioned by oxidatively stressed cell lines of nervous system origin.". J. Neurosci. 18 (18): 7047–60. PMID 9736629.
• Cunningham TJ, Jing H, Wang Y, Hodge L (2000). "Calreticulin binding and other biological activities of survival peptide Y-P30 including effects of systemic treatment of rats.". Exp. Neurol. 163 (2): 457–68. doi:10.1006/exnr.2000.7390. PMID 10833321.
• Cunningham TJ, Jing H, Akerblom I; et al. (2002). "Identification of the human cDNA for new survival/evasion peptide (DSEP): studies in vitro and in vivo of overexpression by neural cells.". Exp. Neurol. 177 (1): 32–9. doi:10.1006/exnr.2002.7979. PMID 12429208.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Porter D, Weremowicz S, Chin K; et al. (2003). "A neural survival factor is a candidate oncogene in breast cancer.". Proc. Natl. Acad. Sci. U.S.A. 100 (19): 10931–6. doi:10.1073/pnas.1932980100. PMC 196905. PMID 12953101.
• Zhang Z, Henzel WJ (2005). "Signal peptide prediction based on analysis of experimentally verified cleavage sites.". Protein Sci. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
• Suzuki Y, Yamashita R, Shirota M; et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
• Monitto CL, Dong SM, Jen J, Sidransky D (2005). "Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia.". Clin. Cancer Res. 10 (17): 5862–9. doi:10.1158/1078-0432.CCR-04-0435. PMID 15355918.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Lai YP, Peng YF, Zuo Y; et al. (2005). "Functional and structural characterization of recombinant dermcidin-1L, a human antimicrobial peptide.". Biochem. Biophys. Res. Commun. 328 (1): 243–50. doi:10.1016/j.bbrc.2004.12.143. PMID 15670776.
• Rieg S, Steffen H, Seeber S; et al. (2005). "Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo.". J. Immunol. 174 (12): 8003–10. doi:10.4049/jimmunol.174.12.8003. PMID 15944307.
• Watchorn TM, Dowidar N, Dejong CH; et al. (2006). "The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes.". Int. J. Oncol. 27 (4): 1105–11. doi:10.3892/ijo.27.4.1105. PMID 16142329.
• Lowrie AG, Wigmore SJ, Wright DJ; et al. (2006). "Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues.". Br. J. Cancer 94 (11): 1663–71. doi:10.1038/sj.bjc.6603148. PMC 2361319. PMID 16685272.
• Ewing RM, Chu P, Elisma F; et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Frum R, Busby SA, Ramamoorthy M; et al. (2007). "HDM2-binding partners: interaction with translation elongation factor EF1alpha.". J. Proteome Res. 6 (4): 1410–7. doi:10.1021/pr060584p. PMID 17373842.
• Lee Motoyama JP, Kim-Motoyama H, Kim P; et al. (2007). "Identification of dermcidin in human gestational tissue and characterization of its proteolytic activity.". Biochem. Biophys. Res. Commun. 357 (4): 828–33. doi:10.1016/j.bbrc.2007.03.112. PMID 17448443.

External links

• Dermcidins at the US National Library of Medicine Medical Subject Headings (MeSH)